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Protective effects of salvianolic acid A on clozapine-induced cardiotoxicity in zebrafish
Shenghua Lin1, Cailian Mo1, Luyi Yan2
1Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan, China.
Abstract:
The clinical use of clozapine (CLZ), an atypical antipsychotic drug, was affected by side effects, such as cardiotoxicity. We selected normally developing zebrafish embryos to explore the antagonism of salvianolic acid A (SAA) against clozapine-induced cardiotoxicity. Embryos were treated with CLZ and SAA, and zebrafish phenotypes were observed at 24 h, 48 h, 72 h, and 96 h after treatment. The observed phenotypes included heart shape, heart rate, and venous sinus-arterial bulb (SV-BA) interval. Real-time quantitative PCR was used to detect changes in the expression of genes involved in heart inflammation, oxidative stress, and apoptosis. The results showed that SAA relieved pericardial edema, increased heart rate, and reduced the SV-BA interval. The PCR results also showed that when the zebrafish embryos were incubated with SAA and CLZ for 96 h, the expression of il-1b and nfkb2 were significantly downregulated, the expression of sod1 and cat were significantly upregulated, and the expressions of mcl1a and mcl1b were significantly downregulated. In summary, SAA can antagonize clozapine-induced cardiotoxicity.
Insights
Salvianolic acid A (SAA) effectively counteracts clozapine-induced cardiotoxicity in zebrafish embryos. This natural compound mitigates heart damage by reducing inflammation and oxidative stress, offering a potential therapeutic strategy.
Area of Science:
- Pharmacology
- Cardiovascular Toxicology
- Zebrafish Embryology
Background:
- Clozapine (CLZ), an atypical antipsychotic, exhibits cardiotoxicity, limiting its clinical use.
- Understanding mechanisms to mitigate CLZ-induced heart damage is crucial for patient safety.
Purpose of the Study:
- To investigate the protective effects of salvianolic acid A (SAA) against clozapine-induced cardiotoxicity.
- To elucidate the molecular pathways involved in SAA's cardioprotective action.
Main Methods:
- Zebrafish embryos were exposed to CLZ and SAA.
- Phenotypic assessments included heart shape, heart rate, and SV-BA interval.
- Gene expression analysis (real-time qPCR) focused on inflammation, oxidative stress, and apoptosis markers.
Main Results:
- SAA treatment ameliorated CLZ-induced pericardial edema and normalized heart rate.
- SAA significantly reduced the SV-BA interval, indicating improved cardiac function.
- SAA modulated gene expression, downregulating inflammatory (il-1b, nfkb2) and apoptotic (mcl1a, mcl1b) markers, while upregulating antioxidant genes (sod1, cat).
Conclusions:
- Salvianolic acid A demonstrates significant antagonism against clozapine-induced cardiotoxicity in a zebrafish model.
- SAA's protective effects are mediated through the suppression of inflammatory and apoptotic pathways and enhancement of antioxidant defenses.
